Abstract
Spine function requires precise control of the actin cytoskeleton. Kalirin-7, a GDP/GTP exchange factor for Rac1, interacts with PDZ proteins such as PSD-95, colocalizing with PSD-95 at synapses of cultured hippocampal neurons. PSD-95 and Kalirin-7 interact in vivo and in heterologous expression systems. In primary cortical neurons, transfected Kalirin-7 is targeted to spines and increases the number and size of spine-like structures. A Kalirin-7 mutant unable to interact with PDZ proteins remains in the cell soma, inducing local formation of aberrant filopodial neurites. Kalirin-7 with an inactivated GEF domain reduces the number of spines below control levels. These results provide evidence that PDZ proteins target Kalirin-7 to the PSD, where it regulates dendritic morphogenesis through Rac1 signaling to the actin cytoskeleton.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 229-242 |
| Number of pages | 14 |
| Journal | Neuron |
| Volume | 29 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2001 |
Funding
Dr. Anthony Lanahan and Dr. Paul Worley (Department of Neuroscience, The Johns Hopkins University) generously provided the rat hippocampus/cortex cDNA library. We thank Dr. Dezhi Liau and Bing Ye for providing cultures of cortical neurons. We thank Jee Hae Kim (Department of Neuroscience, The Johns Hopkins University) for useful advice. We thank Kirsten Barnes for her help with the yeast two-hybrid screen. We thank Dr. Henry Keutmann (Endocrine Unit, Massachusetts General Hospital) for the synthesis of the antigenic peptide. We thank Marie Bell, Kate Deanehan, and Lixian Jin for general laboratory assistance. This work was supported by NIH grants DA-00266 and DK-32948.
ASJC Scopus subject areas
- General Neuroscience